Based on substantial evidence that an infectious agent or agents may play a role in the etiology of at least a subtype of schizophrenic illness, we are searching for evidence of an infectious or toxic substance in schizophrenic brains. Studies undertaken to date include immunocytochemical investigations for antigens to cytomegalovirus (CMV), herpes simplex virus (HSV), varicella virus, rubella and mumps. Although sporadic cases have shown positive results with immunocytochemical studies, these have been inconsistent and rare. We have also undertaken in situ hybridization probes for CMV, and cultivation of schizophrenic and control brain specimens on cultures of human and non-human neural tissue. Using special stains for glia we have evaluated the brains of guinea pigs and primates previously innoculated with schizophrenic and control brain tissue. During the past year we have investigated the effects of cerebrospinal fluid and sterile brain tissue from schizophrenic patients on the growth, peptide production and morphology of cultured human neuroblastoma cells. Changes in growth rate have thus far been noted following treatment of cells with fresh CSF from two schizophrenic cases. The remaining samples studied to date (six schizophrenic, seven normals) have shown no changes in any of the three parameters under study and no other differences between normals and schizophrenics have emerged.